nature.com/articles/s4141…

Remarkable study, showing that when tumors get big enough and have high enough glycolysis rates, they can consume so much glucose as to induce systemic hypoglycemia and extreme lactate elevations. Effect was accentuated by the drug, but present before. I would expect his type of observation in mice SC xenografts, where tumor mass can be ~25% of the animal, but this is the first time I ever saw a report like this in humans.

While our studies are ultimately directed at translating therapies to the clinic, along the way, we have made some interesting biochemical observations.

A very surprising finding from our work is that as little as 3% of normal Enolase activity is sufficient for viability.

https://twitter.com/Muller_Lab/status/1331089662648217601

This gets at the phenomenon of threshold toxicity in metabolic toxicity/diseases.

To begin with, glioma cells with 1p36 / ENO1 - homozygous deletions loose >90% Enolase activity - because ENO1 is the major isoform of Enolase in the cell.

Why does chemotherapy kill cancerous but not normal cells? Most cancer biologists would answer this by stating that chemotherapy is selectively toxic to proliferating cells, and that cancer cell proliferate more than normal cells. Not exactly - there's a lot more to it.

https://twitter.com/trendscancer/status/1321125361602695168

Many normal tissues, like bone marrow and gut cells are actually more proliferative than even the most aggressive cancers. E.g. pro-myelocytes have a doubling time of around 17 hrs whilst even aggressive epithelial tumors double every 2-3 weeks or so.